Sex Hormone Binding Globulin (SHBG): Function and Clinical Significance
Sex hormone binding globulin (SHBG) is a glycoprotein that binds and transports sex steroids, particularly testosterone and estradiol, in the bloodstream and regulates their bioavailability to target tissues.
What SHBG Measures
SHBG is a serum glycoprotein primarily synthesized in the liver that:
- Binds with high affinity to 17β-hydroxysteriod hormones, particularly testosterone and estradiol 1
- Regulates the distribution of sex hormones between protein-bound and free (bioactive) states 2
- Serves as a transport protein for sex steroids in plasma 1
- Influences the bioavailability of sex hormones to target tissues 3
Clinical Significance of SHBG Measurement
SHBG measurement is clinically valuable for:
- Calculating free or bioavailable testosterone when total testosterone is near lower limits 4
- Evaluating mild disorders of androgen metabolism 1
- Identifying women with hirsutism who are more likely to respond to estrogen therapy 1
- Assessing androgen-estrogen balance in gonadal and sexual dysfunctions 5
- Serving as a potential marker for insulin resistance and cardiovascular risk 5
Factors Affecting SHBG Levels
Conditions that Increase SHBG
- Hyperthyroidism
- Hypogonadism
- Androgen insensitivity
- Hepatic cirrhosis (in men)
- Aging
- HIV/AIDS
- Smoking 2
Conditions that Decrease SHBG
- Hypothyroidism
- Obesity
- Acromegaly
- Cushing's disease
- Insulin resistance (Metabolic syndrome/Type 2 diabetes)
- Non-alcoholic fatty liver disease
- Nephrotic syndrome 2
Medications Affecting SHBG Levels
- Increasing SHBG: Anticonvulsants, estrogens, thyroid hormones 2
- Decreasing SHBG: Growth hormone, glucocorticoids, testosterone, anabolic androgenic steroids 2
Clinical Applications
In Male Hypogonadism
- SHBG measurement is essential when total testosterone is borderline low or when SHBG alterations are suspected 4
- Helps distinguish between primary and secondary hypogonadism when evaluated alongside LH and FSH 4
- Patients with compensated hypogonadism may have normal/high total testosterone but low free testosterone due to elevated SHBG 4
In Liver Disease
- SHBG levels typically rise in chronic liver disease, though they may decline with progression from compensated to decompensated cirrhosis 2
- In men with advanced liver disease, elevated SHBG contributes to reduced free testosterone despite potentially normal total testosterone levels 2
In Polycystic Ovary Syndrome (PCOS)
- SHBG measurement helps in calculating Free Androgen Index (FAI), which is a reliable biomarker for diagnosing biochemical hyperandrogenism in PCOS 2
- Low SHBG levels are common in PCOS and contribute to increased free testosterone levels 2
Measurement Considerations
- Traditional immunoassay methods are widely available but may have limitations in accuracy 6
- LC-MS/MS methods are emerging as more accurate alternatives for SHBG quantification 6
- When interpreting testosterone levels, SHBG should be considered to properly assess the bioactive hormone fraction 4
Common Pitfalls in SHBG Interpretation
- Relying solely on total testosterone without considering SHBG levels can miss cases of hypogonadism in men with elevated SHBG 4
- FAI calculations can be inaccurate if SHBG concentration is <30 nmol/L 2
- SHBG levels fluctuate with various conditions and medications, requiring careful interpretation in clinical context 2
- Failure to consider SHBG when evaluating sex hormone status may lead to misdiagnosis of endocrine disorders 3
In summary, SHBG is not merely a carrier protein but plays a crucial role in regulating sex hormone bioavailability and serves as an important biomarker in various endocrine, metabolic, and liver disorders.